Perfluoroalkyl substances and risk of type II diabetes: A prospective nested case-control study
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BACKGROUND: Perfluoroalkyl substances (PFAS) have drawn much attention due to bioaccumulation potential and their current omnipresence in human blood. We assessed whether plasma PFAS, suspected to induce endocrine-disrupting effects, were prospectively associated with clinical type 2 diabetes (T2D) risk. METHODS: We established a nested case-control study within the Swedish prospective population-based Västerbotten Intervention Programme cohort. Several PFAS were measured in plasma from a subset of 124 case-control pairs at baseline (during 1990-2003) and at 10-year follow-up. T2D cases were matched (1:1) according to gender, age and sample date with participants without T2D (controls). Conditional logistic regressions were used to prospectively assess risk of T2D by baseline PFAS plasma concentrations. Associations between long-term PFAS plasma levels (mean of baseline and follow-up) and insulin resistance (HOMA2-IR) and beta-cell function (HOMA2-B%) at follow-up were prospectively explored among 178 and 181 controls, respectively, by multivariable linear regressions. RESULTS: After adjusting for gender, age, sample year, diet and body mass index, the odds ratio of T2D for the sum of PFAS (Σ z-score PFAS) was 0.52 (95% confidence interval, CI: 0.20, 1.36), comparing third with first tertile; and 0.92 (95% CI: 0.84, 1.00) per one standard deviation increment of sum of log-transformed PFAS. Among the controls, the adjusted β of HOMA2-IR and HOMA-B% for the sum of PFAS were -0.26 (95% CI: -0.52, -0.01) and -9.61 (95% CI: -22.60, 3.39) respectively comparing third with first tertile. CONCLUSIONS: This prospective nested case-control study yielded overall inverse associations between individual PFAS and risk of T2D, although mostly non-significant. Among participants without T2D, long-term PFAS exposure was prospectively associated with lower insulin resistance.
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Several prospective cohort studies have reported that exposure to PFASs may increase the risk of T2D, as well as the potential positive association with IR.
“Several prospective cohort studies have reported that exposure to PFASs may increase the risk of T2D, as well as the potential positive association with IR (Donat-Vargas et al., 2019; Margolis and Sant, 2021; Roth and Petriello, 2022; Sun et al., 2018).”
From Exposure to per- and polyfluoroalkyl substances in early pregnancy, risk of gestational diabetes mellitus, potential pathways, and influencing factors in pregnant women: A nested case-control study (2023) · cites this paper as Donat-Vargas et al., 2019
The Results and Conclusion report the opposite for this prospective study: PFAS exposure was generally associated with lower T2D risk and lower insulin resistance, not increases in either. The Discussion acknowledges one earlier prospective study with positive T2D associations, but says prospective findings were conflicting and that prospective associations with insulin resistance in another study were null. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThere is limited study linking PFAS exposure to Type 2 diabetes, with low risk and uncertain long-term impact in adults.
“| Diabetes | Limited study about linking to Type 2 diabetes. | Low | Adults | Uncertain long-term impact | [231] |”
From Industrial Applications, Environmental Fate, Human Exposure, and Health Effects of PFAS (2025) · cites this paper as [231]
The Introduction describes the epidemiological evidence linking PFAS exposure to type 2 diabetes as limited and inconsistent. The Conclusion reports no adverse effect in this study and calls for further work to evaluate potential metabolic effects, supporting uncertainty about longer-term impact. It does not establish a generally low diabetes risk for adults; the Introduction also notes studies reporting positive associations. (LLM, conf=0.85)
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- Authors
- Donat-Vargas, C., Bergdahl, I. A., Tornevi, A., Wennberg, M., Sommar, J., Kiviranta, H., Koponen, J., Rolandsson, O., & Åkesson, A.
- Affiliations
- Umeå University (SE)
- Finnish Institute for Health and Welfare (FI)
- Karolinska Institutet (SE)
- Corresponding author
- Åkesson, Agneta
- ORCID
- Venue
- Environment International
- Publisher
- Elsevier BV
- Published
- 2019-02
- Volume
- 123
- Pages
- 390-398
- ISSN
- 0160-4120 (ISSN-L)
- OpenAlex
- W2905062925
- Cited by
- 88
- References
- 50
- Citations by year
- 2026: 5 · 2025: 17 · 2024: 13 · 2023: 13 · 2022: 13 · 2021: 13 · 2020: 9 · 2019: 5
- FWCI
- 3.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Environment International (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DiVA at Umeå University (Umeå University) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Swedish Research Council for Health, Working Life and Welfare (2012-0758)
- Västerbotten County Council
- Swedish Research Council (2017-00822)
- Fundación Ramón Areces
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Fluorine in Organic Chemistry
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- perfluorinated compounds, type 2 diabetes, insulin resistance, beta-cell function, endocrine disruption, plasma PFAS concentrations, long-term exposure
- MeSH terms
- Adult, Diabetes Mellitus, Type 2, Diet, Female, Fluorocarbons, Humans, Insulin Resistance, Male, Middle Aged, Prospective Studies, Sweden, Body Mass Index, Linear Models, Logistic Models, Odds Ratio, Case-Control Studies, Endocrine Disruptors
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